By Lisa Seachrist

Washington Editor

WASHINGTON — Even though the cloning issue reared its ugly head once more with a Chicago physicist vowing to clone a human being before the federal government could ban it, the National Bioethics Advisory Commission (NBAC) focused on its original charge at this week's meeting: developing guidelines for using stored tissues for research.

The genetics subcommittee presented its "work-in-progress" guidelines to the entire committee on Wednesday. Central to the subcommittee's current guidelines was focusing on how researchers intend to use the tissues as the basis for determining the level of consent that must be obtained to make the research ethical.

"One of the problems of the current debate over the use of stored tissues is that it focuses on how the sample is stored," said Ezekiel Emanuel, associate professor of medical ethics at Harvard Medical School, in Boston. "We've changed that focus to whether researchers intend to use the information in an anonymous fashion or in a way that identifies who the tissue comes from."

That distinction, the subcommittee has determined, would allow researchers to use previously stored tissue without the consent of the individual. However, all research on stored tissue would have to go before an institutional review board — a requirement that does not exist under current guidelines.

The exact number of tissue samples currently stored in the United States is not known. The commission offers a conservative estimate of 250 million, with 500 million a likely number. These samples have served as a rich resource for a variety of medical research.

Most Patients Unaware Of Stored Tissues

However, most people don't know that when they sign consent forms to have biopsies and surgeries, they often agree to have the samples stored not only as a reference for their care, but also for parts of those stored tissues to be used for research.

The genetic information that can be culled from these stored tissues is immense. As such, researchers are faced with two preeminent ethical issues when they want to use stored tissues: first, they must devise a method to protect the privacy of the individual whose tissue they are using; and second, they must address how to ethically use tissues for which there is inadequate informed consent.

NBAC member Rhetaugh Dumas, vice provost emerita at the University of Michigan-Ann Arbor, initially balked at the proposal, saying that every attempt should be made to obtain specific informed consent for using the tissues, regardless of the type of research to be performed.

"We are in an era where we are moving to more informed consent. It doesn't seem right to make recommendations to propose research without informed consent," Graves said. "If there is no way to obtain consent we should provide exceptions, but every effort must be made to get consent. But I must say that, in general, I urge consent as the rule."

Obtaining such consent has been opposed by many researchers as too costly and time consuming. Recontacting people for specific consent would require that researchers try to track down people who have moved or who have died. And many patients see such an effort as an intrusion.

Steve Holtzman, chief business officer at Millennium Pharmaceuticals Inc., in Cambridge, Mass., noted that there are two purposes to consent: the first out of respect for a person's autonomy and the second to attempt to protect a research subject from harms.

"We have to weigh the value of research vs. the costs to autonomy," said Holtzman. "If you can protect people against harms, then the value to society outweighs the need for informed consent. By conducting anonymous research you protect against harms."

The subcommittee's willingness to forgo informed consent for existing samples does not, however, hold for clinical samples that would be taken after the guidelines are adopted.

Instead, the subcommittee proposes patients sign a generalized consent that is more detailed than the current consent process and that would allow researchers to use the tissue in an anonymous fashion. Any research where samples can be identified would require detailed and specific consent.

Patricia Barr of the National Action Plan on Breast Cancer has worked on developing a generalized consent procedure for women who are undergoing breast biopsies. Barr told members of NBAC it is important the donor be treated as an active participant in the research process.

"Many people have an interest in doing good, especially when faced with a scary situation," Barr said. "Women facing breast cancer are under a tremendous amount of stress. Signing an agreement to participate in research can give them a sense of control."

In addition to a generalized consent form to be presented to patients several days before a biopsy, Barr's group called for tissue samples to be stored in more centralized collection points than the pathologist's lab.

"Tissue is a limited resource," Barr noted. "You have to prioritize how it is to be used." *